Ex Parte Campillo et al

Board of Patent Appeals and Interferences

Jun 2, 2010

11218295 (B.P.A.I. Jun. 2, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte ELENA DEL CAMPILLO and DAMIAN CRAWFORD
____________

Appeal 2009-011502
Application 11/218,295
Technology Center 1600
____________

Decided: June 2, 2010
____________

Before ERIC GRIMES, DEMETRA J. MILLS, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the appeal under 35 U.S.C. § 134 by the Patent
Applicant from the Patent Examiner’s rejections of claims 1-11, 18, and 19
in U.S. Application 11/218,295. The Board’s jurisdiction for this appeal is
under 35 U.S.C. § 6(b). We affirm-in-part.

Appeal 2009-011502
Application 11/218,295

STATEMENT OF THE CASE
The claims in this appeal all involve a DNA comprising the sequence
of SEQ ID NO: 1 which serves as a promoter for AtCel5, an endo-beta-1,4-
glucanase, isolated from Arabidopsis thaliana (Spec. 2:12-14 & 14:17-26).
Claims 1-11, 18 and 19 are pending and stand rejected by the
Examiner as follows:
1. Claims 1 and 18 under 35 U.S.C. § 112, first paragraph, as failing
to comply with the written description requirement (Ans. 4);
2. Claims 1 and 18 stand under 35 U.S.C. § 112, first paragraph, for
lack of enablement (Ans. 6);
3. Claims 1-3 and 18 under 35 U.S.C. § 102(b) as anticipated by
Federspiel et al. (GenBank Accession No.: AF000657 (1997)) (Ans. 8); and
4. Claims 1-11, 18, and 19 under 35 U.S.C. § 103 as obvious over
Federspiel, Baszczynski (US 5,401,836, issued Mar. 28, 1995), Schmulling
(US Pub. 2003/0074698 A1, published Apr. 17, 2003), and TAIR
(Microarray Expression Search Result) (Ans. 9).
Claims 1, 2, and 18 are representative and read as follows:
1. An isolated promoter comprising a polynucleotide
sequence having at least about 85% sequence identity to the
polynucleotide sequence of SEQ ID NO: 1 or a fragment
thereof having promoter activity.

2. An isolated promoter wherein said promoter comprises a
polynucleotide sequence having the polynucleotide sequence of
SEQ ID NO: 1 or a fragment thereof having promoter activity
in the root cap.

18. An expression vector comprising an isolated promoter
having a polynucleotide sequence that has at least 85%
sequence identity to a polynucleotide sequence of SEQ ID
NO: 1.
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1. WRITTEN DESCRIPTION REJECTION
Claims 1 and 18 stand rejected under 35 U.S.C. § 112, first paragraph,
as failing to comply with the written description requirement (Ans. 4).
Statement of the issue
The issue in this rejection is whether a genus of promoters with at
least 85% sequence identity to SEQ ID NO: 1 is described in the
Specification.
Principles of Law
For claims to a genus of genetic materials, the Federal Circuit has held
that “a generic statement such as ‘vertebrate insulin cDNA’ or ‘mammalian
insulin cDNA,’ without more, is not an adequate written description of the
genus because it does not distinguish the claimed genus from others, except
by function.” University of California v. Eli Lilly & Co., 119 F.3d 1559,
1568 (Fed. Cir. 1997). Instead, the written description must define the genus
to allow one skilled in the art to “visualize or recognize the identity of the
members of the genus,” e.g., by describing a representative number of
species or a description of “structural features commonly possessed by
members of the genus that distinguish them from others.” Lilly, 119 F.3d at
1568.
As noted in Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d
1313, 1332 (Fed. Cir. 2003), “Eli Lilly did not hold that all functional
descriptions of genetic material necessarily fail as a matter of law to meet
the written description requirement; rather, the requirement may be satisfied
if in the knowledge of the art the disclosed function is sufficiently correlated
to a particular, known structure.”
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Consistent with Lilly and Amgen, in Enzo Biochem, Inc. v. Gen-Probe
Inc., 323 F.3d 956, 964 (Fed. Cir. 2002), it was held that a claimed DNA
could be described without, necessarily, disclosing its structure. The court
adopted the standard that
the written description requirement can be met by “show[ing]
that an invention is complete by disclosure of sufficiently
detailed, relevant identifying characteristics . . . i.e., complete or
partial structure, other physical and/or chemical properties,
functional characteristics when coupled with a known or
disclosed correlation between function and structure, or some
combination of such characteristics.”

Id. at 964.
Facts (“F”)
1. Claims 1 and 18 are directed to an isolated promoter comprising “a
polynucleotide sequence having at least about 85% sequence identity to the
polynucleotide sequence of SEQ ID NO: 1 . . . having promoter activity.”
2. The Specification1 discloses that SEQ ID NO: 1 is the promoter of
AtCel5 (Spec. 2:22-24). SEQ ID NO: 1 is 1405 nucleotides long (Sequence
Listing filed Mar. 23, 2006).
3. A promoter is defined in the Specification as a “polynucleotide molecule”
that “is involved in recognition and binding of RNA polymerase II and other
proteins . . . to initiate transcription” (id. at 4:28 to 5:3).
4. The Specification describes methods for modifying SEQ ID NO: 1 (id. at
6-9).

1 Serial No. 11/218,295, the application involved in this appeal.
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5. The Specification discloses that “promoter fragments may be provided
comprising at least about 30, 50, 70, 90, 110, 125, 150 or about 200 or
longer nucleotides.” (Id. at 9:10-13.)
6. Example 3 of the Specification describes “1400-bp [base pairs] of the
putative promoter plus the 5’ UTR and the ATG translation start of ATCel5”
which was cloned upstream of the GUS gene (id. at 23:5-7).
7. Examples 11-12 showed that the 1400 base pair fragment drove
expression of GUS, a marker protein, in the root tip (id. at 28:15-20).
8. The Specification discloses that the 1400 base pair fragment comprises
sequences which are “common to many actively transcribed plant genes”;
“consensus sequences . . . found in genes up-regulated . . . after
gravistimulation”; and “cis-acting regulatory elements” (Spec. 26:19-29).
9. The Specification does not teach which sequences identified in the 1400
base pair promoter fragment are involved in or necessary for its promoter
activity.
Analysis
To satisfy the written description requirement for a genus of nucleic
acid sequence, one skilled in the art must be able “visualize or recognize the
identity of the members of the genus,” e.g., by providing a description of
“structural features commonly possessed by members of the genus that
distinguish them from others,” describing a representative number of species
within the genus, or showing a correlation between structure and function.
Lilly, 119 F.3d at 1568; Enzo, 323 F.3d at 964. These principles were
recently reaffirmed in Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598
F.3d 1336 (Fed. Cir. 2010).
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The Examiner correctly determined that the claimed genus of
promoters comprising “at least about 85% sequence identity to the
polynucleotide sequence of SEQ ID NO: 1” and “having promoter activity”
was not described in the Specification. The Specification describes only a
single example of a promoter of SEQ ID NO: 1, a 1400 base pair fragment
which was used to express the GUS gene product (F6-F7). The
Specification describes the complete nucleotide sequence of the 1400 base
pair fragment, and points to certain sequences within it (F8), but the
Specification does not establish that any of these sequences are involved in
or necessary for its promoter activity in initiating RNA transcription (F9),
the defined activity for a promoter (F3). Thus, a representative number of
species of the claimed genus has not been described and a correlation was
not shown between the promoter sequence structure and its transcriptional
activity. Consequently, the evidence supports the Examiner’s determination
that the claimed promoter genus was not described in the Specification.
Appellants contend that “one can immediately envision sequences that
have the stated degree of identity with the disclosed sequence” (App. Br. 4).
This argument is not persuasive because while the skilled worker might be
able to “envision” sequences with “at least about 85% sequence identity
to . . . SEQ ID NO: 1,” there is no evidence that the worker could envision
sequences with the recited amount of identity which have “promoter
activity,” the invention which is claimed. Appellants have not established
those sequences which are necessary for the claimed promoter to have
transcriptional activity.
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Appellants contend that a promoter sequence is disclosed to have as
few as 30 base pairs and that the likelihood of selecting sequences
possessing promoter activity is therefore high (Reply Br. 3).
Section 112, first paragraph, requires that the claimed invention be
described. A high likelihood of selecting a sequence with promoter activity
does nothing to illuminate a description of the claimed genus that would
distinguish it structurally from other groups of sequences. It is true that the
written description requirement does not demand that every member of a
genus be described, but an inventor is still charged with the duty of
disclosing “either a representative number of species falling within the scope
of the genus or structural features common to the members of the genus so
that one of skill in the art can ‘visualize or recognize’ the members of the
genus.” Ariad Pharmaceuticals Inc., 598 F.3d at 1370.

2. ENABLEMENT REJECTION
Claims 1 and 18 stand rejected under 35 U.S.C. § 112, first paragraph,
as not enabling the claimed genus of sequences having at least 85% identity
to SEQ ID NO: 1 and promoter activity (Ans. 6).
Statement of the issue
The issue in this rejection is whether the Specification enabled the full
scope of claims 1 and 18.
Principles of law
“[T]o be enabling, the specification . . . must teach those skilled in the
art how to make and use the full scope of the claimed invention without
‘undue experimentation.’” In re Wright, 999 F.2d 1557, 1561 (Fed. Cir.
1993).
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“When rejecting a claim under the enablement requirement of section
112, the PTO bears an initial burden of setting forth a reasonable explanation
as to why it believes that the scope of protection provided by that claim is
not adequately enabled by the description of the invention provided in the
specification of the application . . . .” Id. at 1561-1562.
“That some experimentation may be required is not fatal; the issue is
whether the amount of experimentation required is ‘undue.’” In re Vaeck,
947 F.2d 488, 495 (Fed. Cir. 1991) (emphasis in original).

Facts
10. The Specification describes several different ways of selecting or
making sequences having 85% identity to SEQ ID NO: 1 (Spec. 6:1 to 9:3).
11. The Specification describes an example in which a promoter sequence is
used to drive expression of a gene (id. at 22:25 to 23:12; 27:12 to 30:23).
12. The Specification states that a person of ordinary skill in the art was
familiar with “specific conditions and procedures for the construction,
manipulation, and isolation of . . . polynucleotide molecules . . . and the
screening and isolation of polynucleotide molecules.” (Id. at 8:28-9:3.)

Analysis
The Examiner had the burden of establishing that the claimed
invention was not adequately enabled by the Specification. This burden was
not met. The Specification describes how sequences having 85% identity to
the promoter of SEQ ID NO: 1 would be identified and tested for promoter
activity (F10-12). Persons of ordinary skill in the art were familiar with
isolating polynucleotides and testing for their activity (F11 & F12). Thus,
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Appellants’ argument that only routine screening would be required to select
promoter sequences within the scope of the claim is supported by the
evidence.
Citing Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361 (Fed. Cir.
1997), the Examiner contends that “one skilled in the art is left to randomly
produce an endless number of substitutions or other changes to nucleotides
from SEQ ID NO:1, and test each new molecule for having promoter
activity, which is undue experimentation.” (Ans. 7.)
In Genentech Inc. v. Nordisk, A/S, 108 F.3d at 1367, there was
evidence that the claimed technology was “unpredictable” and “in the early
stages of development.” No such evidence has been provided in this case by
the Examiner. Consequently, the facts in Genentech Inc. v. Nordisk, A/S
differ from those of record in this case and the enablement rejection is
reversed.

3. ANTICIPATION by FEDERSPIEL
Claims 1-3 and 18 stand rejected under 35 U.S.C. § 102(b) as
anticipated by Federspiel (Ans. 8).
Statement of the issue
The issue in this rejection is: 1) whether the term “isolated promoter”
embraces the AtCel5 promoter sequence on a BAC clone as in claim 1; and
2) whether a BAC clone is an expression vector as in claim 18.

Facts
13. Federspiel is a sequence listing from GenBank of a 92,948 base pair
sequence of DNA from Arabidopsis thaliana.
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14. The sequence is of a BAC (bacterial artificial chromosome) clone
carrying the Arabidopsis DNA.
15. The sequence is annotated with coding sequences (CDS) and mRNA
joining sites.
16. The Examiner found, and Appellants did not dispute, that F19G10.16 on
page 7-8 of Federspiel corresponds to the AtCel5 gene.
17. Federspiel did not describe nor annotate the presence of promoter
sequences in the GenBank listing.
18. Appellants did not dispute that SEQ ID NO: 1 was present in
Federspiel’s sequence listing in GenBank.
19. Federspiel did not identify SEQ ID NO: 1 as a promoter.

Analysis
Claims 1-3
Claims 1-3 are directed to “[a]n isolated promoter” which comprises a
polynucleotide sequence having the sequence of SEQ ID NO:1 or a
sequence with at least 85% identity to it.
It is undisputed that Federspiel describes SEQ ID NO:1, albeit amidst
a string of 92,948 nucleotides.
The Examiner contends that the term “isolated” would be understood
to mean that the promoter sequence is “isolated” from the chromosome on
which it normally resides (Ans. 16). Appellants contend, that “it is clear
[from reading the Specification] that the word ‘isolated’ was intended to
convey a nucleic acid molecule which would be useful in the expression of
transgenes in plants.” (Reply Br. 8.)
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Appellants ask us to read the term “isolated” to mean that the
promoter is in a size and form that would make it operable to cause
expression of a gene to which it is joined. This is not the broadest
reasonable interpretation of the term as it would be understood by persons of
ordinary skill in the art in light of the Specification.
The term “isolated” or “isolated promoter” is not defined in the
Specification. There is no evidence that “isolated” was intended to mean a
fully functional promoter of a size and form capable of being operably
linked to a gene whose expression is desired. Rather, the term appears to be
used conventionally to mean that it “isolated” or “derived” from another
DNA fragment, such as isolated from the chromosome on which it normally
resides.
The Specification states that the invention relates to “constructs” and
“expression vectors” in which the promoter is “operably linked to a
transcribable polynucleotide molecule” (Spec. 3:1-3 & 23-24). Thus, while
such vectors and constructs would be reasonably interpreted to comprise a
promoter in a size and form in which it can be operably linked to a gene
whose expression is desired, there is no evidence that the term “isolated
promoter” alone has this meaning. Appellants’ narrow interpretation is not
supported by the Specification.
Appellants also contend that claim 1 “cannot be reasonably read to
encompass an entire chromosome” (App. Br. 8).
Federspiel discloses a bacterial artificial chromosome, known by its
abbreviation “BAC.” The 92,948 base pair DNA is an artificial construct
comprising vector material and a DNA fragment from the Arabidopsis
thaliana genome (Ans. 16; F13-14). The product disclosed by Federspiel is
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therefore not a natural product, but an artificial one constructed from two
sources of DNA. We discern no language in the claim which would exclude
claim 1 from reading on an artificial chromosome.
For the foregoing reason, we affirm the anticipation rejection of claim
1.

Claim 18
Claim 18 is directed to an expression vector comprising an isolated
promoter “having a polynucleotide sequence that has at least 85% sequence
identity to a polynucleotide of SEQ ID NO: 1.”
The term “expression vector” is not described in the Specification, but
persons of ordinary skill in the art would have understood it, in the light of
the Specification, to mean a vector comprising a promoter, where a cloned
gene is placed under control of the promoter.2 The Examiner did not
introduce evidence that the BAC DNA described by Federspiel is an
expression vector in which a gene could be introduced into it and controlled
by the AtCel5 promoter. Consequently, we reverse the rejection of claim 18.

4. OBVIOUSNESS REJECTION
Claims 1-11, 18, and 19 stand rejected under 35 U.S.C. § 103(a) as
obvious over Federspiel, Baszczynki, Schmulling, and TAIR (Ans. 3)

2 Zaid A., Hughes, H.G., Porceddu, E. & Nicholas, F., Glossary of
biotechnology and genetic engineering (1999). FAO Research and
Technology Paper 7. Rome: Food and Agriculture Organization of the
United Nations.
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Statement of the issue
The issue in this rejection is whether it would have been obvious to
persons of ordinary skill in the art to have modified Baszczynski and
Schmulling based on the teachings of Federspiel and TAIR.
Facts
20. The experiment described under “AtGenExpress,” and labeled as
Exhibit A in the Evidence Appendix attached to the Appeal Brief, states that
“TAIR stopped accepting new microarray data submissions in June 2005.”
21. The Examiner finds that a TAIR Microarray Expression Search shows
that At1g22880 shows expression in the root (Answer 10). Appellants do
not challenge the Examiner’s finding that At1g22880 corresponds to the
AtCel5 gene.
22. As shown in Exhibit B in the Evidence Appendix attached to the Appeal
Brief, data in TAIR, expression of numerous different genes was measured.
Among the numerous gene, gene 264775_at, which is corresponds to
AT1G22880 or AtCel5, is listed on page 189 (App. Br. 14).

Analysis
The Examiner found on page 10 of the Answer:
A 1597 bp intergenic region upstream of the ORF of beta-
glucanase gene [AtCel5] (F19G10.16) and downstream of the
ORF of F19G10.17 gene was also identified according to the
annotation of the BAC sequence. The intergenic region shows
100% identity to the SEQ ID NO: 1.
. . .
TAIR microarray expression search result suggests that
AtCel5 (also known as At1g22880) gene is highly expressed in
root including under the drought or cold stress condition (data
searchable online since Jan. 2005).
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Based on these findings, the Examiner determined that it would have
been obvious to a person with ordinary skill in the art to modify the
expression methods of Baszczynski or Schmulling “by replacing the
promoters with the intergenic region of Federspiel et al., resulting in the
instant inventions. . . . One would have been motivated to do so given that
root expression of the genes of” Baszczynski and Schmulling “are desirable,
and that the intergenic region of Federspiel et al. is an obvious choice as a
root promoter as suggested by TAIR microarray expression search result.”
(Ans. 11).
The Examiner did not establish prima facie obviousness. The “1597
bp intergenic region” corresponding to SEQ ID NO: 1 was not annotated by
Federspiel as suggested by the Examiner on page 10 of the Answer.
Federspiel annotated the coding sequences of the various genes present in
the BAC clone, including their mRNA joining sites (F15), but Federspiel did
not annotate or identify intergenic regions (F17). It is not disputed that the
SEQ ID NO: 1 promoter region is disclosed in Federspiel’s sequence listing,
but it only appears amidst a continuous 92,948 base pair long nucleotide
listing, without special emphasis or annotation.
Sufficient evidence was also not presented that AtCel5 is “highly
expressed in root.” (Ans. 10.) It is not clear upon which data this
conclusion was made. For example, on page 189 of a TAIR experiment
(F22), AtCel5 is shown to have a value of “90,” but there are 9 values higher
and 6 values lower on just this one page of data. The relationship between
these numbers and expression levels was not articulated in the Answer.
The conclusion that “the intergenic region of Federspiel et al. is an
obvious choice as a root promoter as suggested by TAIR microarray
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expression search result” (Ans. 11) is not supported by the evidence of
record. Federspiel did not specifically identify this intragenic region, let
alone characterize it as a promoter. TAIR describes the expression of the
complete AtCel5 gene (F21), but does not teach the promoter region of SEQ
ID NO: 1 as responsible for the expression pattern. The Examiner did not
identify a fact-based reason to have isolated the promoter sequence from the
BAC clone and then use it in an expression construct. (Id. at 11.)

SUMMARY
The rejection of claims 1 and 18 under § 112, first paragraph, for lack
of written description is affirmed.
The rejection of claim 1 and 18 under § 112, first paragraph, for
failing to provide an enabling disclosure is reversed.
The anticipation rejection of claim 1 is affirmed. Claims 2 and 3 were
not separately argued and fall with claim 1. 37 C.F.R. § 41.37(c)(vii)(1).
The anticipation rejection of claim 18 is reversed.
The obviousness rejection of claims 1-11, 18, and 19 is reversed.

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED-IN-PART

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16
Application/Control No.

11/218,295
Applicant(s)/Patent Under
Reexamination
Elena Del. Campillo et al.
Notice of References Cited
Examiner

Li Zheng
Art Unit

1600

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Zaid A., Hughes, H.G., Porceddu, E. & Nicholas, F., Glossary of biotechnology and genetic
engineering (1999). FAO Research and Technology Paper 7. Rome: Food and Agriculture
Organization of the United Nations.

V

W

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*A copy of this reference is not being furnished with this Office action. (See Manual of Patent Examining Procedure, Section 707.05(a).)
**APS encompasses any electronic search i.e. text, image, and Commercial Databases.
U.S. Patent and Trademark Office
PTO-892 (Rev. 03-98) Notice of References Cited Part of Paper No. 16
expression vector A cloning vector that has been constructed in such a way that, after
insertion of a DNA molecule, its coding sequence is properly transcribed and the RNA is
translated. The cloned gene is put under the control of a promoter sequence for the
initiation of transcription, and often also has a transcription termination sequence at its
end. Such promoters are termed high level; examples include P1 (the leftward promoter
of phage l) and the promoter of the yeast PGK (phosphoglycerate kinase) gene.

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